Rhodium-catalyzed [4+1] annulation of sulfoxonium ylides: Sequential ortho-C[sbnd]H functionalization/carbonyl α-amination toward polycyclic quinazolinones

Article abstract of DOI:10.1016/j.tetlet.2020.152441

A rhodium-catalyzed [4+1] annulation between 2-aryl quinazolin-4(3H)-ones and sulfoxonium ylides was developed, leading to 12-aroyl isoindolo[1,2-b]quinazolin-10(12H)-ones in moderate to good yields. This reaction proceeds with sequential ortho-C[sbnd]H functionalization of 2-aryl quinazolin-4(3H)-ones and an intramolecular rhodium-catalyzed α-amination of carbonyl to furnish the cyclization. This procedure was applied to access some 13-aroyl luotonin A derivatives whereby the direct construction of ring c.

Full text of DOI:10.1016/j.tetlet.2020.152441

Tetrahedron Letters xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rhodium-catalyzed [4+1] annulation of sulfoxonium ylides: Sequential
ortho-CAH functionalization/carbonyl a-amination toward polycyclic
quinazolinones
Chang Wang a, Peng-Cheng Qian b, Fan Chen b, Jiang Cheng a,b,
⇑
a School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, and Jiangsu Province Key Laboratory of Fine Petrochemical
Engineering, Changzhou University, Changzhou 213164, PR China
b College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A rhodium-catalyzed [4+1] annulation between 2-aryl quinazolin-4(3H)-ones and sulfoxonium ylides
was developed, leading to 12-aroyl isoindolo[1,2-b]quinazolin-10(12H)-ones in moderate to good yields.
This reaction proceeds with sequential ortho-CAH functionalization of 2-aryl quinazolin-4(3H)-ones and
Received 29 August 2020
Accepted 1 September 2020
Available online xxxx
an intramolecular rhodium-catalyzed a-amination of carbonyl to furnish the cyclization. This procedure
was applied to access some 13-aroyl luotonin A derivatives whereby the direct construction of ring c.
Keywords:
Ó 2020 Elsevier Ltd. All rights reserved.
Rhodium-catalyzed
Sulfoxonium ylides
2-Aryl quinazolin-4(3H)-ones
Introduction
eq 2) [11]. We also developed rhodium-catalyzed reaction of sul-
Being polycyclic N-containing compounds, isoindolo[1,2-b]
quinazolin-10(12H)-one frameworks are ubiquitous in pharma-
ceutical compounds and natural products, such as luotonin A, B
and E [1], 14-azacamptothecin [2], as well as belotecan (CKD-
602) (Fig. 1) [3]. Undoubtedly, the construction of the ring C
(Scheme 3) is the pivot to access the aforementioned frameworks,
including radical domino cyclizations [4], Pd-catalyzed sequential
cyanation/N-addition/N-arylation of 2-bromo-N-(2-iodobenzyl)-
benzamides [5], palladium-catalyzed carbonylation of 2-bro-
foxonium ylides and anthranils toward indoloindolones involving
a [4+1] annulation (Scheme 1, eq 3) [12]. Thus, isoindoline motif
in tetracyclic quinazolinones may be constructed whereby a simi-
lar [4+1] annulation between 2-aryl quinazolin-4(3H)-ones and
sulfoxonium ylides triggered by the transition metal-catalyzed
chelation-assisted ortho-CAH functionalization (Scheme 1, eq 4).
However, this strategy faces big challenge in the followed cycliza-
tion step, where the rhodium-catalyzed intramolecular
tion of ketone has never been reported before [13,14].
a-amina-
mobenzylamines with 2-bromoanilines [6], and CuI/
L
-proline-cat-
Herein, we wish to report our study on the rhodium-catalyzed
[4+1] annulation between 2-aryl quinazolin-4(3H)-ones and sul-
foxonium ylides, proceeding with the sequential chelation-assisted
ortho-CAH functionalization and a rhodium-catalyzed a-amination
of carbonyl.
We initiated our work via exploring the reaction of 2-
phenylquinazolin-4(3H)-one 1a (0.1 mmol) and sulfoxonium ylide
2a (0.15 mmol) in DCE under N2 atmosphere at 120 °C for 12 h
(Table 1). Disappointingly, [Cp*Rh(MeCN)3](SbF6)2, [Cp*IrCl2]2 and
[Cp*RhCl2]2 resulted in no reaction (entries 1–3). To our delight,
the annulation product 3aa was isolated in 10% yield in the pres-
ence of Cp*Rh(OAc)2ÁH2O (5 mol %) and AgSbF6 (50 mol %, entry
4). Among the Ag(I) tested, AgNO3 (20%) was superior to Ag2CO3
(13%), AgOAc (11%) and AgOTf (<5%, entries 5–8). The reaction effi-
ciency was further improved by adding Cu(II) as co-additives (33–
56%, 2 equiv, entries 9–13) and Cu(OAc)2ÁH2O was the best (56%,
entry 13). The solvent also have a profound effect in the reaction
alyzed consecutive Sonogashira coupling and hydroamination
cyclization [7]. Nevertheless, the development of facile procedures
starting from readily available material was far below expected.
Recently, we had witnessed much progress in the application of
aroyl sulfoxonium ylides as novel carbene surrogates in organic
synthesis [8,9]. Among which, many elegant examples were
reported on the rhodium-carbene involved sequential CAH func-
tionalization to access cyclic products, where ylides served as C2
synthons (Scheme 1, eq 1) [10]. Alternatively, sulfoxonium ylides
also served as C1 synthons in [4+1] annulation toward a series of
heterocyclic products whereby ortho-CAH functionalization and
the followed annulation of the methene in ylide with double
bonds, such as N@N, and C@N to furnish the cyclization (Scheme 1,
⇑
Corresponding author.
E-mail address: jiangcheng@cczu.edu.cn (J. Cheng).
https://doi.org/10.1016/j.tetlet.2020.152441
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: C. Wang, P. C. Qian, F. Chen et al., Rhodium-catalyzed [4+1] annulation of sulfoxonium ylides: Sequential ortho-CAH function-
alization/carbonyl -amination toward polycyclic quinazolinones, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2020.152441
a

C. Wang et al.
Tetrahedron Letters xxx (xxxx) xxx
Fig. 1. Representive Polycyclic Quinazolinones Derivatives.
Scheme 2. The Scope of Sulfoxonium Ylides. a Reaction conditions: 2-phenylquina-
zolin-4(3H)-one 1a (0.1 mmol), sulfoxonium ylide 2 (0.15 mmol), Cp*Rh(OAc)2ÁH2O
(5 mol %), AgNO3 (50 mol %), Cu(OAc)2ÁH2O (0.5 equiv), DCE (2.0 mL), N2 (1.0 atm),
at 120 °C for 12 h, in a sealed Schlenk tube.
Scheme 1. Reaction of Aroyl Sulfoxonium Ylides.
Table 1
Selected results for screening the optimized reaction conditions.a
Entry
Catalyst
Ag(i)
Additive
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
[Cp*Rh(MeCN)3]X2
[Cp*RhCl2]2
[Cp*IrCl2]2
–
–
–
–
–
–
–
–
–
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
n.r.
n.r.
n.r.
10
13
11
<5
20
46
36
33
35
AgSbF6
AgSbF6
AgSbF6
Ag2CO3
AgOAc
AgOTf
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
Cp*Rh(OAc)2ÁH2O
9
CuCl2
CuSO4
CuCO3
Cu(OTf)2
Cu(OAc)2ÁH2O
10
11
12
13
56, 43c,31d,78e
a
Reaction conditions: 2-phenylquinazolin-4(3H)-one 1a (0.1 mmol), sulfoxonium ylide 2a (0.15 mmol), catalyst (5 mol %), Ag(I) (50 mol %), indicated Cu(II) additives (2
b
c
d
e
equiv), DCE (2.0 mL), N2 (1.0 atm.), at 120 °C for 12 h, in a sealed Schlenk tube, X = SbF6. Isolated yields. Toluene, PhCl, Cu(OAc)2ÁH2O (0.5 equiv), n.r. = no reaction.
2

C. Wang et al.
Tetrahedron Letters xxx (xxxx) xxx
Scheme 5. The mechanism study.
a
Scheme 3. The Scope of 2-Arylquinazolin-4(3H)-ones. Reaction conditions: 2-
arylquinazolin-4(3H)-one 1 (0.1 mmol), sulfoxonium ylide 2a (0.15 mmol), Cp*Rh
(OAc)2ÁH2O (5 mol %), AgNO3 (50 mol %), Cu(OAc)2ÁH2O (0.5 equiv), DCE (2.0 mL), N2
(1.0 atm), at 120 °C for 12 h, in a sealed Schlenk tube.
efficiency. DCE (56%) was superior to toluene (43%) and PhCl (31%).
Importantly, reducing the ratio of Cu(OAc)2ÁH2O to 0.5 equivalent
further increased the reaction yield to 78% (entry 13). The structure
of 3aa coordinated with one molecular of CHCl3 was further con-
firmed by X-ray crystal analysis [15].
Scheme 6. A Tentative Mechanism.
summarized in Scheme 2. Generally, the catalytic system was not
sensitive to the position of substituted group in the aryl of sulfox-
onium ylides ring since both para- (3ab-ae, 60–74%; 3al, 45%),
meta- (3af, 64%; 3ag, 71%), and ortho- (3ah, 70%) analogues all
worked well under the procedure. Importantly, the reaction toler-
ated some functional groups, such as methyl (3ab, 69%; 3af, 64%),
tert-butyl (3ac, 60%), fluoro (3ad, 74%; 3ag, 71%), trifluoromethyl
(3ae, 62%) and cyclohexyl (3am, 56%), which provided correspond-
ing product in moderate to good yield. Disappointingly, substrate
possessing nitro did not work under the reaction conditions. Par-
ticularly, 2-thiophenyl analogue worked well, providing 3aj in
69% yield.
With the optimized reaction conditions in hand, firstly, the
scope and limitation of sulfoxonium ylides were tested, as
Subsequently, the substrate scope of 2-arylquinazolin-4(3H)-
one was also investigated. As shown in Scheme 3, once again, all
the substrates ran smoothly under the procedure. It tolerates
tert-butyl (3ba, 63%), methyl (3ca, 69%; 3fa, 55%; 3ia, 48%), and tri-
fluoromethyl (3ea, 51%) in the cyclized phenyl ring. However, the
para- (3da, 45%) and ortho- (3ga, 43%) chloride analogues provide
the corresponding fused N-containing heterocyclic products in rel-
ative low yields. No regioisomer of 3ia was detected by GC–MS,
and the cyclization preferred to take place in the ortho-position
of phenyl with less hindrance.
To improve the practicability of the procedure, the reaction was
conducted in 1 mmol scale and 3aa was isolated in an acceptable
65% yield. Moreover, this [4+1] reaction was applied to access
13-aroyl luotonin A derivatives whereby the direct construction
of ring c (Scheme 4) [16]. To our delight, a series of luotonin A
derivatives was isolated in moderate yields (38%-51%). The ring D
in luotonin
A frameworks was pre-constructed during the
synthesis of 2-(quinolin-2-yl)quinazolin-4(3H)-one starting from
commercially available 2-aminobenzamide and quinoline-2-car-
baldehyde. Thus, this procedure represents a facile, efficient and
rapid pathway leading to 13-aroyl luotonin A derivatives.
a
Scheme 4. The Application to Access 13-Aroyl Luotonin A Derivatives. Reaction
conditions: 2-arylquinazolin-4(3H)-one
1 (0.1 mmol), sulfoxonium ylide 2a
(0.15 mmol), Cp*Rh(OAc)2ÁH2O (5 mol %), AgNO3 (50 mol %), Cu(OAc)2ÁH2O (0.5
equiv), DCE (2.0 mL), N2 (1.0 atm), at 120 °C for 12 h, in a sealed Schlenk tube.
3

C. Wang et al.
Tetrahedron Letters xxx (xxxx) xxx
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More control experiments were conducted to get some insights
into this transformation. As shown in Scheme 5 (see Supporting
Information for detail), the H/D exchange experiment revealed
80% of ortho-D in d5-1a was replaced with H, leading to d3-1a. Thus,
the cleavage of the ortho-CAH in 1a was reversible.
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On the basis of the aforementioned discussion and some relative
previous works [17], a tentative mechanism is outlined in Scheme 6.
First, the reaction starts with the depolymerization of rhodium cat-
alyst and CAH activation with 2-phenylquinazolin-4(3H)-one to
access a five-membered rhodacyclic intermediate A. Second, the
insertion of benzoyl sulfoxonium ylide to the five-membered rho-
dacyclic intermediate A leads to intermediate B, which releases
one molecular of DMSO to access rhodium carbene intermediate
C. Then intermediate C transforms into a six-membered rhodacycle
D through intramolecular migration. Third, this key intermediate D
takes part in reductive elimination to furnish the [4+1] products,
along with the formation of Rh(I), which is oxidized by Cu(II) and
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In conclusion, we have developed a rhodium-catalyzed [4+1]
annulation between 2-aryl quinazolin-4(3H)-ones and sulfoxo-
nium ylides, leading to 12-benzoyl isoindolo[1,2-b]quinazolin-10
(12H)-ones in moderate to good yields. The reaction proceeds with
sequential ortho-CAH activation of 2-aryl quinazolin-4(3H)-ones
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and an intramolecular rhodium-catalyzed carbonyl
a-amination.
Importantly, the practicability of this [4+1] was further improved
by the application in facile accessing 13-aroyl luotonin A deriva-
tives whereby the direct construction of ring C.
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Declaration of Competing Interest
(c) X. Shi, R. Wang, X. Zeng, Y. Zhang, H. Hu, C. Xie, M. Wang, Adv. Synth. Catal.
360 (2018) 4049;
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
(d) Y. Xu, G. Zheng, X. Yang, X. Li, Chem. Commun. 54 (2018) 670;
(e) G. Zheng, M. Tian, Y. Xu, X. Chen, X. Li, Org. Chem. Front. 5 (2018) 998;
(f) P. Hu, Y. Zhang, Y. Xu, S. Yang, B. Liu, X. Li, Org. Lett. 20 (2018) 2160;
(g) Y. Xiao, H. Xiong, S. Sun, J. Yu, J. Cheng, Org. Biomol. Chem. 16 (2018) 8715;
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Acknowledgements
(i) G.L. Hoang, A.D. Streit, J.A. Ellman, J. Org. Chem. 83 (2018) 15347;
(j) C.F. Liu, M. Liu, L. Dong, J. Org. Chem. 84 (2019) 409.
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(2019) 4039;
We thank the National Natural Science Foundation of China
(nos. 2971025), ‘‘Innovation & Entrepreneurship Talents” Introduc-
tion Plan of Jiangsu Province, Jiangsu Key Laboratory of Advanced
Catalytic Materials & Technology (BM2012110) and Advanced
Catalysis and Green Manufacturing Collaborative Innovation Cen-
ter for financial supports.
(b) C. Wu, J. Zhou, G. He, H. Li, Q. Yang, R. Wang, Y. Zhou, H. Liu, Org. Chem.
Front. 6 (2019) 1183;
(c) H. Oh, S. Han, A.K. Pandey, S.H. Han, N.K. Mishra, S. Kim, R. Chun, H.S. Kim,
J. Park, I.S. Kim, J. Org. Chem. 83 (2018) 4070.
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[15] Crystallographic data for 3aa (CCDC 1938013).
Appendix A. Supplementary data
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Org. Chem. 29 (2009) 1533;
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.152441.
(b) A. Witt, J. Bergman, Curr. Org. Chem. 7 (2003) 659.
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[18] One reviewer suggested an alternative mechanism: after the production of
intermediate D (Scheme 5), D might be protonated to give the ArCH2COPh
intermediate. Then transition metal (Rh, Ag or Cu) mediated C-N
intramolecular oxidative coupling between the NH and CH2CO parts could
give the products 3.
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